Sunday, August 28, 2016

Declining trend in the utilization of adjuvant radiation.

A recent report in European Urology found that in spite of three randomized clinical trials (RCTs) that proved the efficacy of immediate or adjuvant radiation following surgery with adverse pathology results compared to a wait-and-see approach, a lower%age of such patients are getting adjuvant treatment. Why should this be?

I refer readers to a recent discussion of the issues involved, which I won’t fully reiterate here. First, let’s look at the report by Sineshaw et al. The authors examined the records of 97,270 patients in the National Cancer Database where patients were found to have adverse pathological features (pT3/4 or positive surgical margins) in the period from 2005-2011. What they found is this:

·      Postoperative RT utilization declined from 9.1% to 7.3%.
·      Utilization declined with age: 8.5% in patients aged 18–59 to 6.8% in patients aged 70–79. 
·      Utilization was 14% at community cancer programs compared to 7% at teaching/research centers.
·      Among those with stage pT3/4, utilization was 17% if they had positive margins, but 7% if they had negative margins.
·      Utilization was 17% among those with pathology Gleason score of 8-10 compared to 4% among those with Gleason score  of 6 or less.

First, a note about the timeframe examined in their study: only one of the three RCTs  (Thompson et al. 2009) was published in that timeframe. The Bolla et al. study was not published until 2012, and the Wiegel et al. study was not presented until 2013. The AUA/ASTRO guidelines advocating adjuvant radiation were not issued until 2013. So in the timeframe examined in their study, we would not expect to see the full impact of those three studies and the new guidelines. This conflicts with the statement made in the publication:
In a retrospective analysis of 97 270 patients with prostate cancer, we showed that use of postoperative radiotherapy for adverse pathologic features has declined over time after the publication of findings from major randomized clinical trials and consensus guidelines supporting consideration of such therapy.”

A report in Medscape included comments from some illustrious radiation oncologists that are worth noting:
·      Jeffrey Michalski  (Washington University, St. Louis) echoed the authors’ anachronistic lament that doctors were not following the evidence in the RCTs and guidelines.
·      Anthony D’Amico (Dana-Farber and Brigham and Women’s Hospital) pointed out that only one of the RCTs showed an advantage in metastasis-free and overall survival. He further explained that multiple risk factors may be a better indication for adjuvant radiation.
·      Michael Zelefsky (MSKCC) noted that we don’t yet know if waiting for rising PSA would have any worse outcomes.
·      Howard Sandler (Cedars-Sinai) blamed low utilization on urologists who don’t immediately refer adverse pathology patients to radiation oncologists. They are not given options or provided with expertise.

Until the results of ongoing clinical trials on the benefit of early salvage radiation become available, this remains a difficult decision. A patient with adverse pathology should immediately begin discussions with a radiation oncologist, preferably at a teaching/research hospital, so that he fully understands what the risks and benefits are of waiting.

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